Isolation and Biological Evaluation of Alfa-Mangostin as Potential Therapeutic Agents against Liver Fibrosis

Yi-Jen Liao; Chun-Ya Lee; Yuh-Ching Twu; Fat-Moon Suk; Tzu-Chieh Lai; Ya-Ching Chang; Yi-Cheng Lai; Jing-Wei Yuan; Hong-Ming Jhuang; Huei-Ruei Jian; Li-Chia Huang; Kuang-Po Chen; Ming-Hua Hsu

doi:10.3390/bioengineering10091075

Bioengineering (Sep 2023)

Isolation and Biological Evaluation of Alfa-Mangostin as Potential Therapeutic Agents against Liver Fibrosis

Yi-Jen Liao,
Chun-Ya Lee,
Yuh-Ching Twu,
Fat-Moon Suk,
Tzu-Chieh Lai,
Ya-Ching Chang,
Yi-Cheng Lai,
Jing-Wei Yuan,
Hong-Ming Jhuang,
Huei-Ruei Jian,
Li-Chia Huang,
Kuang-Po Chen,
Ming-Hua Hsu

Affiliations

Yi-Jen Liao: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Chun-Ya Lee: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Yuh-Ching Twu: Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Fat-Moon Suk: Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
Tzu-Chieh Lai: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Ya-Ching Chang: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Yi-Cheng Lai: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Jing-Wei Yuan: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Hong-Ming Jhuang: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Huei-Ruei Jian: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Li-Chia Huang: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan
Kuang-Po Chen: Department of Chemistry, Chinese Culture University, Taipei 111, Taiwan
Ming-Hua Hsu: Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan

DOI: https://doi.org/10.3390/bioengineering10091075
Journal volume & issue: Vol. 10, no. 9
p. 1075

Abstract

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The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted α-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated α-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of α-mangostin on Transforming growth factors-beta 1 (TGF-β1) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). α-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of α-mangostin was assessed by carbon tetrachloride (CCl4) treatment mouse model. The data showed that α-mangostin treatment inhibited TGF-β1-induced Smad2/3 phosphorylation and alpha-smooth muscle actin (α-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, α-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in α-mangostin-treated HSCs. The CCl4-induced liver fibrosis mouse model showed that the administration of α-mangostin significantly decreased the expression of the fibrosis markers (α-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that α-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, α-mangostin may be used as a potential novel therapeutic agent against liver fibrosis.

Published in Bioengineering

ISSN: 2306-5354 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology; Science: Biology (General)
Website: https://www.mdpi.com/journal/bioengineering

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